title: Fine mapping the TAGAP risk locus in rheumatoid arthritis.
abstract: A common allele at the TAGAP gene locus demonstrates a suggestive, but not conclusive association with risk of rheumatoid arthritis (RA). To fine map the locus, we conducted comprehensive imputation of CEU HapMap single-nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS) of 5,500 RA cases and 22,621 controls (all of European ancestry). After controlling for population stratification with principal components analysis, the strongest signal of association was to an imputed SNP, rs212389 (P=3.9 × 10(-8), odds ratio=0.87). This SNP remained highly significant upon conditioning on the previous RA risk variant (rs394581, P=2.2 × 10(-5)) or on a SNP previously associated with celiac disease and type I diabetes (rs1738074, P=1.7 × 10(-4)). Our study has refined the TAGAP signal of association to a single haplotype in RA, and in doing so provides conclusive statistical evidence that the TAGAP locus is associated with RA risk. Our study also underscores the utility of comprehensive imputation in large GWAS data sets to fine map disease risk alleles.
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: R
authors.initials: R
authors.lastname: Chen
authors.forename: E A
authors.initials: EA
authors.lastname: Stahl
authors.forename: F A S
authors.initials: FA
authors.lastname: Kurreeman
authors.forename: P K
authors.initials: PK
authors.lastname: Gregersen
authors.forename: K A
authors.initials: KA
authors.lastname: Siminovitch
authors.forename: J
authors.initials: J
authors.lastname: Worthington
authors.forename: L
authors.initials: L
authors.lastname: Padyukov
authors.forename: S
authors.initials: S
authors.lastname: Raychaudhuri
authors.forename: R M
authors.initials: RM
authors.lastname: Plenge
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D020690:GTPase-Activating Proteins / Q000235:genetics*; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D020690:GTPase-Activating Proteins; C557017:TAGAP protein, human